Variant: NM_000527.5(LDLR):c.2101G>A (p.Gly701Ser)

CA023635

183130 (ClinVar)

Gene: LDLR

Condition: hypercholesterolemia, familial

Inheritance Mode: Semidominant inheritance

UUID: 4ce3f966-2bbf-4b29-ad24-d066a9b9ef76

Approved on: 2021-06-18

Published on: 2021-06-24

HGVS expressions

NM_000527.5:c.2101G>A
NM_000527.5(LDLR):c.2101G>A (p.Gly701Ser)
ENST00000558518.6:c.2101G>A
ENST00000252444.9:n.2355G>A
ENST00000455727.6:c.1597G>A
ENST00000535915.5:c.1978G>A
ENST00000545707.5:c.1606+250G>A
ENST00000557933.5:c.2101G>A
ENST00000558013.5:c.2101G>A
ENST00000558518.5:c.2101G>A
NM_000527.4:c.2101G>A
NM_001195798.1:c.2101G>A
NM_001195799.1:c.1978G>A
NM_001195800.1:c.1597G>A
NM_001195803.1:c.1606+250G>A
NM_001195798.2:c.2101G>A
NM_001195799.2:c.1978G>A
NM_001195800.2:c.1597G>A
NM_001195803.2:c.1606+250G>A
NC_000019.10:g.11120483G>A
CM000681.2:g.11120483G>A
NC_000019.9:g.11231159G>A
CM000681.1:g.11231159G>A
NC_000019.8:g.11092159G>A
NG_009060.1:g.36103G>A

Uncertain Significance

• Met criteria codes: PP1_Moderate PP3

• Not Met criteria codes: BS4 BS3 BS1 BS2 BP5 BP7 BP2 BP3 BP4 BP1 BA1 PVS1 PM6 PM2 PM3 PM1 PM4 PM5 PS2 PS4 PS3 PS1 PP4 PP2

Expert Panel

Familial Hypercholesterolemia VCEP

Criteria Specification Information

Evidence submitted by expert panel

Familial Hypercholesterolemia VCEP

NM_000527.5(LDLR):c.2101G>A (p.Gly701Ser) variant is classified as variant of Uncertain significance for Familial Hypercholesterolemia by applying evidence codes (PP1_Moderate and PP3) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PP1_moderate - Variant segregates with FH phenotype in 4 informative meioses in 2 families from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation). PP3 - REVEL: 0,754.

Met criteria codes

• PP1_Moderate: Variant segregates with FH phenotype in 4 informative meioses in 2 families from Molecular Genetics Laboratory (Centre for Cardiovascular Surgery and Transplantation).
• PP3: REVEL: 0,754. Score is above 0,75.

Not Met criteria codes

• BS4: No non-segregations were identified/found.
• BS3: No functional assays performed/found - not applicable.
• BS1: FAF = 0.0002447 (0.02447%) in Latino exomes (gnomAD v2.1.1). FAF is not above 0.2%.
• BS2: No unaffected individuals identified with the variant.
• BP5: Not applicable.
• BP7: Missense variant. Not applicable.
• BP2: Not identified in individuals with other variants.
• BP3: Not applicable.
• BP4: REVEL: 0,754. Score is not below 0,50.
• BP1: Not applicable.
• BA1: FAF = 0.0002447 (0.02447%) in Latino exomes (gnomAD v2.1.1). FAF is not above 0.5%
• PVS1: Missense variant. Not applicable.
• PM6: No de novo cases were identified.
• PM2: PopMax MAF = 0.0004233 (0.042%) in Latino exomes (gnomAD v2.1.1). MAF is not below 0.02%.
• PM3: Not identified in individuals with other variants.
• PM1: Missense at codon 701 - it is not exon 4 or any of the 60 Cys residues listed and does not meet PM2. Not applicable.
• PM4: Missense variant. Not applicable.
• PM5: No other variant found in this codon in ClinVar database (assessed 4 June 2020).
• PS2: No de novo cases were identified.
• PS4: PM2 is not met. Not applicable.
• PS3: No functional assays performed/found - not applicable.
• PS1: No variant described that leads to the same amino acid change.
• PP4: PM2 is not met. Not applicable.
• PP2: Not applicable.